Biocompatible copper sulfide-based nanocomposites for artery interventional chemo-photothermal therapy of orthotropic hepatocellular carcinoma.

Transcatheter arterial embolization has been considered as a promising targeted delivery approach for hepatocellular carcinoma (HCC). Currently, chemoembolization was the main treatment for unresectable HCC. However, the traditional chemoembolization treatment suffers from undesirable therapeutic effects and serious side-effects. In this study, the doxorubicin (DOX)-encapsulated and near-infrared (NIR)-responsible copper sulfide (CuS)-based nanotherapeutics was developed for magnetic resonance imaging (MRI)-guided chemo-photothermal therapy of HCC tumor in rats. The DOX-loaded CuS nanocomposites (DOX@BSA-CuS) demonstrated distinct NIR-triggered drug release behavior and high photothermal effect. In an orthotopic HCC rat model, DOX@BSA-CuS nanocomposites were selectively delivered to the tumor site via the intra-arterial transcatheter. The proposed DOX@BSA-CuS nanocomposites plus NIR laser irradiation exhibited significant tumor growth suppression performance. Moreover, the treatment progress can be monitored by MRI images. Finally, the preliminary toxicity estimate suggested the negligible side-effect of DOX@BSA-CuS nanocomposites during the therapeutic process. These results suggest the clinical translational potential possibility for imaging-guided arterial embolization with DOX@BSA-CuS nanocomposites for the treatment of HCC.

[Construction and effect evaluation of tuberculosis information platform in Ningxia].

Objective: To explore the value of information technology in management of tuberculosis patients. Methods: The data comes from the case reports of Ningxia tuberculosis patients in the national tuberculosis special report system from March to December 2019 and the data of Ningxia tuberculosis information management platform. Using the computer Information and communication technologies and the Internet platform, unified data collection and data interface standards,Hospital Information System(HIS) of 18 (90%)TB specific Hospitals in Ningxia 22 counties are linked together, forming a closed loop management System, to realize Information interconnection, compare the patients' diagnostic rate before and after the application, and standardize treatment differences. Results: The system automatically collected and uploaded valid data for 2 918 times, and the consistency rate of uploaded data was 94.8%.The clinical diagnostic rate was 18.23% (1 154/6 332) before and 39.1% (914/2 335) after using the AI imaging screening subsystem (χ²=235.56, P<0.001).The regular medication rate of patients after system use was 86.89% (510/587), which was higher than that before [73.72% (544/738)] (χ²=3.94, P<0.05).The cure rate of etiologically positive tuberculosis patients (2019) was 86.03% (788/916), which was higher than that of 83.45% (1 008/1 208) before the use of the system (2018) (χ²=435.43, P<0.001). Conclusion: The tuberculosis information management platform in Ningxia has achieved tuberculosis information interconnection, significantly improving the standard diagnosis, treatment and management level of tuberculosis.

[Quantitative study on the development of fetal ventricles and cisterna magna in second and third trimesters with MRI].

Objective: To analyze the changes of growth and development of normal fetal ventricles and cisterna magna with gestational age(GA) and the correlation with fetal gender in the second and third trimester,and establish the MR prenatal diagnosis reference standards. Methods: A total of 633 fetuses (mean GA (27.0±4.1) weeks (18.9-40.6 weeks))without central nervous system abnormalities were retrospectively collected from the Obstetrics and Gynecology Hospital of Fudan University from June 2012 to August 2017. The lateral ventricle trigonometric width (LVTW), third ventricle width (TVW), fourth ventricle width (FVW), anterior-posterior diameter of the fourth ventricle(APDFV), cavum septum pellucidum width (CSPW) and cisterna magna width (CMW) were obtained in the standard measure planes on MR image.The correlation between the biometrics and GA and the correlation between the biometrics and fetal gender were analyzed respectively, and the normal reference values of the biometrics were calculated. Spearman correlation analysis, Pearson correlation analysis,linear regression analysis, independent samples t-test and paired samples t-test were used for statistic analysis. Results: (1)Fetal LLVTW,RLVTW,TVW,CSPW and CMW in second and third trimesters were correlated with GA at medium and low levels(the correlation coefficient r were 0.311, 0.277, 0.207, 0.226, 0.295, respectively, all P<0.01). FVW and APDFV were statistically correlated with GA, and the linear regression equations were as follows: y=0.022×GA-0.043 (adjusted R(2)=0.642); y=0.018×GA-0.159 (adjusted R(2)=0.690). (2)Fetal LLVTW,RLVTW,FVW,APDFV and CSPW were not correlated with fetal gender in second and third trimesters(r=-0.078,-0.057,-0.087,-0.004 and 0.024, P=0.124,0.258,0.085,0.931 and 0.618, all P>0.05). TVW and CMW were statistically correlated with fetal gender(r=-0.310, -0.180, P=0.000, 0.006, all P<0.05). (3) The mean values of LLVTW and RLVTW were (0.71±0.13) cm and (0.68±0.13) cm, respectively, and significant difference was found between them(t=3.180, P=0.002). The mean value of CSPW was (0.59±0.15) cm. And the mean values of male and female fetuses for TVW and CMW were (0.17±0.05) cm, (0.16±0.06) cm and (0.68±0.15) cm, (0.58±0.15) cm, respectively. The corresponding prenatal MRI diagnostic criteria were as follows: LLVTW 1.1 cm, RLVTW 1.0 cm, CSPW 1.0 cm, TVW 0.3 cm, CMW (male 1.1 cm, female 1.0 cm). Conclusions: The normal fetal ventricles and cisterna magna are increased with the GA in the second and third trimesters. TVW and CMW are related to fetal gender. The establishment of normal reference values of fetal ventricles and cisterna magna based on GA and fetal gender are conducive to enhance the accuracy of MRI prenatal diagnosis.

Nanodiamonds as pH-switchable oxidation and reduction catalysts with enzyme-like activities for immunoassay and antioxidant applications.

Nanodiamonds (NDs) have recently become a focus of interest from the viewpoints of both science and technology. Their intriguing properties make them suitable as biologically active substrates, in biosensor applications as well as diagnostic and therapeutic biomedical imaging probes. Here, we demonstrate that NDs, as oxidation and reduction catalysts, possess intrinsic enzyme mimetic properties of oxidase, peroxidase and catalase, and these behaviors can be switched by modulating the pH value. NDs not only catalyze the reduction of oxygen (O2) and hydrogen peroxide (H2O2) at acidic pH, but also catalyze the dismutation decomposition of H2O2 to produce O2 at alkaline pH. It was proposed that the molecular mechanism of their peroxidase-like activity is electron-transfer acceleration, the source of which is likely derived from oxygen containing functional groups on their surface. Based on the color reaction, a nanodiamond-based enzyme linked immunosorbent assay (ELISA) was established for the detection of immunoglobulin G (IgG). Surprisingly, NDs display an excellent antioxidant activity due to the protective effect against H2O2-induced cellular oxidative damage. These findings make NDs a promising enzyme mimetic candidate and expand their applications in biocatalysis, bioassays and nano-biomedicine.

Inhibition of invasion and migration of prostate cancer cells by miRNA-509-5p via targeting MDM2.

Prostate cancer is a common malignancy of the male reproductive-urinary system. MDM2 is an oncogene, whose expression can be regulated by microRNA (miRNA). The present study investigated the expression and correlation of miRNA-509-5p and MDM2 to determine the mechanism of their function in invasion and migration of prostate cancer cells. RT-PCR was performed to detect the expression of miRNA-509-5p and MDM2 in tumor, tumor-adjacent, and normal tissues, obtained from prostate cancer patients, using the HGC-27 cell line as an in vitro model. Cultured HGC-27 cells were transfected with miRNA-509-5p mimics, miRNA-509-5p inhibitor, and mimic control. Expression levels of miRNA-509-5p and MDM2 were quantified by RT-PCR. Cell proliferation and invasion/migration were examined by the MTT and transwell assays, respectively. MiRNA-509-5p was significantly down-regulated in prostate cancer cells exhibiting high MDM2 mRNA levels. MiRNA mimic transfection elevated miRNA levels and suppressed MDM2 expression. With prolonged incubation time, the proliferation ratio and OD values of miRNA-509-5p mimic transfected cells decreased, along with decrease in cell migration and invasion. These results suggested that miRNA-509-5p negatively regulates MDM2 expression via targeting the 3'-UTR of genes. As a novel tumor suppressor, miRNA-509-5p in prostate cancer HGC-27 cells can suppress MDM2 expression and inhibit cell proliferation, invasion, and migration. Therefore, miRNA-509-5p could be used as a novel therapeutic agent in the treatment of prostate cancer.

Ultrahigh relaxivity and safe probes of manganese oxide nanoparticles for in vivo imaging.

Mn-based nanoparticles (NPs) have emerged as new class of probes for magnetic resonance imaging due to the impressive contrast ability. However, the reported Mn-based NPs possess low relaxivity and there are no immunotoxicity data regarding Mn-based NPs as contrast agents. Here, we demonstrate the ultrahigh relaxivity of water protons of 8.26 mM(-1) s(-1) from the Mn3O4 NPs synthesized by a simple and green technique, which is twice higher than that of commercial gadolinium (Gd)-based contrast agents (4.11 mM(-1) s(-1)) and the highest value reported to date for Mn-based NPs. We for the first time demonstrate these Mn3O4 NPs biocompatibilities both in vitro and in vivo are satisfactory based on systematical studies of the intrinsic toxicity including cell viability of human nasopharyngeal carcinoma cells, normal nasopharyngeal epithelium, apoptosis in cells and in vivo immunotoxicity. These findings pave the way for the practical clinical diagnosis of Mn based NPs as safe probes for in vivo imaging.

Biochemical and morphological studies of steady state and lipopolysaccaride treated bovine articular cartilage explant cultures.

Explants of bovine articular cartilage were cultured for up to 50 days in 20% fetal calf serum in the presence or absence of the endotoxin lipopolysaccharide (LPS); or in various protocols involving different treatment times with LPS followed by recovery times in the absence of LPS. Cultures were measured in terms of rates of proteoglycan synthesis (incorporation of [35S]sulfate), proteoglycan contents and collagen contents. Histological sections were prepared for both light and electron microscopy. In fetal calf serum, the rates of synthesis and contents of proteoglycans per collagen remained constant, while for LPS treated cultures both parameters decreased. For recovery groups, the rates of proteoglycan synthesis increased during the time of recovery if the LPS treatment times were relatively short (2 weeks or less) and if the tissue was obtained from younger animals; net increase in proteoglycan contents occurred infrequently if at all during recovery protocols. Histological examinations revealed that chondrocytes in cultures maintained in fetal calf serum appeared normal with large stores of glycogen. In LPS treated cultures, chondrocytes were depleted of glycogen stores and contained numerous lipid droplets. In recovery cultures, chondrocytes replenished their glycogen contents, but the lipid droplets remained. For both LPS treated and recovery groups the extracellular matrix was depleted of proteoglycans with time in culture. The results provide further evidence for the ability of this explant culture system to maintain steady state metabolic parameters for proteoglycan metabolism over long time periods and for its utility to study reagents which regulate or perturb these parameters.